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J Immunol. 2014 Jul 15;193(2):564-70. doi: 10.4049/jimmunol.1400825. Epub 2014 Jun 13.

Site-specific chemokine expression regulates central nervous system inflammation and determines clinical phenotype in autoimmune encephalomyelitis.

Author information

1
Department of Neurology, Holtom-Garrett Program in Neuroimmunology and Multiple Sclerosis Center, University of Michigan School of Medicine, Ann Arbor, MI 48109; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI 48109; and.
2
Department of Neurology, Holtom-Garrett Program in Neuroimmunology and Multiple Sclerosis Center, University of Michigan School of Medicine, Ann Arbor, MI 48109;
3
Department of Neurology, Holtom-Garrett Program in Neuroimmunology and Multiple Sclerosis Center, University of Michigan School of Medicine, Ann Arbor, MI 48109; Graduate Program in Immunology, University of Michigan School of Medicine, Ann Arbor, MI 48109; and Neuroscience Program, University of Michigan School of Medicine, Ann Arbor, MI 48109 bmsegal@umich.edu.

Abstract

The adoptive transfer of myelin-reactive T cells into wild-type hosts results in spinal cord inflammation and ascending paralysis, referred to as conventional experimental autoimmune encephalomyelitis (EAE), as opposed to brainstem inflammation and ataxia, which characterize disease in IFN-γRKO hosts (atypical EAE). In this article, we show that atypical EAE correlates with preferential upregulation of CXCL2 in the brainstem, and is driven by CXCR2-dependent recruitment of neutrophils. In contrast, conventional EAE is associated with upregulation of CCL2 in the spinal cord, and is driven by recruitment of monocytes via a partially CCR2-dependent pathway. This study illustrates how regional differences in chemokine expression within a target organ shape the spatial pattern and composition of autoimmune infiltrates, leading to disparate clinical outcomes.

PMID:
24928987
PMCID:
PMC4091641
DOI:
10.4049/jimmunol.1400825
[Indexed for MEDLINE]
Free PMC Article

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